1. Field of the Invention
The invention relates to a topical composition for use as a medicament for the treatment of actinic keratosis.
2. Discussion of the Prior Art
Actinic keratosis is a carcinoma in situ of the epidermis. It concerns a proliferation of transformed keratinocytes restricted to the epidermis, which is characterized by a high rate of mutation of inter alia the tumor suppresser gene p53 and the telomerase gene. It is further associated with characteristic chromosomal aberrations which are typically also found in invasive squamous cell carcinomas of the skin. In about 10% of all patients suffering from actinic keratosis, and particularly in about 30% of the patients with additional immune suppression, a squamous cell carcinoma of the skin develops during the further development of the condition. Thus, a diagnosis of actinic keratosis generally constitutes an indication for treatment.
In the therapy of actinic keratosis, different surgical and physical methods such as cryosurgery, curettage, excision therapy, laser therapy and soft X-ray therapy have been described. Moreover, different forms of pharmacotherapy for the treatment of actinic keratosis are known. For instance, cyclooxygenase inhibitors such as diclofenac, anti-metabolites such as 5′-fluorouracil and immune modulators such as imiquimod have been used for the treatment of actinic keratoses.
Pharmacotherapy of actinic keratosis is often effected by topical application of the corresponding drugs, particularly in the form of water based creams and gels or in the form of alcoholic solutions.
Regarding water based cream and gel formulations known in the state of the art, it has been found to be disadvantageous that these formulations have to be rubbed into the skin. In the process of rubbing in a cream or gel formulation, an active agent comprised therein is typically distributed over a large area of skin. Therefore, it is hardly possible to apply water based cream or gel formulations specifically to the skin areas actually in need of treatment. With respect to alcoholic solutions, it has been found that these formulations tend to run, particularly in the application to head and face areas where actinic keratosis occur particularly often. Thus, alcoholic solutions are not amenable to accurate dosing of active agents either. Because of their inadequate suitability for specific dosing, formulations according to the state of the art are contacted with unnecessarily large areas of skin which increases the degree and risk of side effects. Furthermore, it has been found that drugs such as 5′-fluorouracil tend to crystallize out from aqueous or alcoholic formulation when stored in that form for a period of time corresponding to the typical shelf life of such formulations. WO-A-96/32112 discloses compositions for treating actinic damage to the skin comprising 5′-fluorouracil, a superficial skin peeling agent and a pharmaceutically acceptable carrier, in particular in the form of an alcoholic solution. For the treatment of acute actinic keratoses, 5′-fluorouracil contents of 5 to 10% are suggested. It has been found that topical application of compositions comprising 5′-fluorouracil in these amounts induces substantial side effects. Furthermore, the described alcoholic solution tends to run when topically applied to the surface of the skin.
There is a need for topical compositions suitable for use as a medicament for the treatment of actinic keratosis having high efficiency in the treatment with minimal side effects and allowing for exact dosing.